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Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat

BACKGROUND: There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. trans...

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Autores principales: Semmler-Behnke, Manuela, Lipka, Jens, Wenk, Alexander, Hirn, Stephanie, Schäffler, Martin, Tian, Furong, Schmid, Günter, Oberdörster, Günter, Kreyling, Wolfgang G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445676/
https://www.ncbi.nlm.nih.gov/pubmed/25928666
http://dx.doi.org/10.1186/s12989-014-0033-9
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author Semmler-Behnke, Manuela
Lipka, Jens
Wenk, Alexander
Hirn, Stephanie
Schäffler, Martin
Tian, Furong
Schmid, Günter
Oberdörster, Günter
Kreyling, Wolfgang G
author_facet Semmler-Behnke, Manuela
Lipka, Jens
Wenk, Alexander
Hirn, Stephanie
Schäffler, Martin
Tian, Furong
Schmid, Günter
Oberdörster, Günter
Kreyling, Wolfgang G
author_sort Semmler-Behnke, Manuela
collection PubMed
description BACKGROUND: There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20 nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels. METHODS: We intravenously injected monodisperse, negatively charged, radio-labelled 1.4 nm, 18 nm and 80 nm (198)AuNP at a mass dose of 5, 3 and 27 ?g/rat, respectively, into pregnant rats on day 18 of gestation and in non-pregnant control rats and studied the biodistribution in a quantitative manner based on the radio-analysis of the stably labelled (198)AuNP after 24 hours. RESULTS: We observed significant biokinetic differences between pregnant and non-pregnant rats. AuNP fractions in the uterus of pregnant rats were at least one order of magnitude higher for each particle size roughly proportional to the enlarged size and weight of the pregnant uterus. All three sizes of (198)AuNP were found in the placentas and amniotic fluids with 1.4 nm AuNP fractions being two orders of magnitude higher than those of the larger AuNP on a mass base. In the fetuses, only fractions of 0.0006 (30 ng) and 0.00004 (0.1 ng) of 1.4 nm and 18 nm AuNP, respectively, were detected, but no 80 nm AuNP (<0.000004 (<0.1 ng)). These data show that no AuNP entered the fetuses from amniotic fluids within 24 hours but indicate that AuNP translocation occurs across the placental tissues either through transtrophoblastic channels and/or via transcellular processes. CONCLUSION: Our data suggest that the translocation of AuNP from maternal blood into the fetus is NP-size dependent which is due to mechanisms involving (1) transport through transtrophoblastic channels ¿ also present in the human placenta ¿ and/or (2) endocytotic and diffusive processes across the placental barrier.
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spelling pubmed-44456762015-05-28 Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat Semmler-Behnke, Manuela Lipka, Jens Wenk, Alexander Hirn, Stephanie Schäffler, Martin Tian, Furong Schmid, Günter Oberdörster, Günter Kreyling, Wolfgang G Part Fibre Toxicol Research BACKGROUND: There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20 nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels. METHODS: We intravenously injected monodisperse, negatively charged, radio-labelled 1.4 nm, 18 nm and 80 nm (198)AuNP at a mass dose of 5, 3 and 27 ?g/rat, respectively, into pregnant rats on day 18 of gestation and in non-pregnant control rats and studied the biodistribution in a quantitative manner based on the radio-analysis of the stably labelled (198)AuNP after 24 hours. RESULTS: We observed significant biokinetic differences between pregnant and non-pregnant rats. AuNP fractions in the uterus of pregnant rats were at least one order of magnitude higher for each particle size roughly proportional to the enlarged size and weight of the pregnant uterus. All three sizes of (198)AuNP were found in the placentas and amniotic fluids with 1.4 nm AuNP fractions being two orders of magnitude higher than those of the larger AuNP on a mass base. In the fetuses, only fractions of 0.0006 (30 ng) and 0.00004 (0.1 ng) of 1.4 nm and 18 nm AuNP, respectively, were detected, but no 80 nm AuNP (<0.000004 (<0.1 ng)). These data show that no AuNP entered the fetuses from amniotic fluids within 24 hours but indicate that AuNP translocation occurs across the placental tissues either through transtrophoblastic channels and/or via transcellular processes. CONCLUSION: Our data suggest that the translocation of AuNP from maternal blood into the fetus is NP-size dependent which is due to mechanisms involving (1) transport through transtrophoblastic channels ¿ also present in the human placenta ¿ and/or (2) endocytotic and diffusive processes across the placental barrier. BioMed Central 2014-09-10 /pmc/articles/PMC4445676/ /pubmed/25928666 http://dx.doi.org/10.1186/s12989-014-0033-9 Text en Copyright © 2014 Semmler-Behnke et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Semmler-Behnke, Manuela
Lipka, Jens
Wenk, Alexander
Hirn, Stephanie
Schäffler, Martin
Tian, Furong
Schmid, Günter
Oberdörster, Günter
Kreyling, Wolfgang G
Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat
title Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat
title_full Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat
title_fullStr Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat
title_full_unstemmed Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat
title_short Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat
title_sort size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445676/
https://www.ncbi.nlm.nih.gov/pubmed/25928666
http://dx.doi.org/10.1186/s12989-014-0033-9
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